Mechanisms of sudden cardiac death: oxidants and metabolism.
Ontology highlight
ABSTRACT:
SUBMITTER: Yang KC
PROVIDER: S-EPMC4458707 | biostudies-literature | 2015 Jun
REPOSITORIES: biostudies-literature
Publications
Mechanisms of sudden cardiac death: oxidants and metabolism.
Yang Kai-Chien KC Kyle John W JW Makielski Jonathan C JC Dudley Samuel C SC
Circulation research 20150601 12
Ventricular arrhythmia is the leading cause of sudden cardiac death (SCD). Deranged cardiac metabolism and abnormal redox state during cardiac diseases foment arrhythmogenic substrates through direct or indirect modulation of cardiac ion channel/transporter function. This review presents current evidence on the mechanisms linking metabolic derangement and excessive oxidative stress to ion channel/transporter dysfunction that predisposes to ventricular arrhythmias and SCD. Because conventional an ...[more]
Similar Datasets
Project description:Afferent and efferent cardiac neurotransmission via the cardiac nerves intricately modulates nearly all physiological functions of the heart (chronotropy, dromotropy, lusitropy, and inotropy). Afferent information from the heart is transmitted to higher levels of the nervous system for processing (intrinsic cardiac nervous system, extracardiac-intrathoracic ganglia, spinal cord, brain stem, and higher centers), which ultimately results in efferent cardiomotor neural impulses (via the sympathetic and parasympathetic nerves). This system forms interacting feedback loops that provide physiological stability for maintaining normal rhythm and life-sustaining circulation. This system also ensures that there is fine-tuned regulation of sympathetic-parasympathetic balance in the heart under normal and stressed states in the short (beat to beat), intermediate (minutes to hours), and long term (days to years). This important neurovisceral/autonomic nervous system also plays a major role in the pathophysiology and progression of heart disease, including heart failure and arrhythmias leading to sudden cardiac death. Transdifferentiation of neurons in heart failure, functional denervation, cardiac and extracardiac neural remodeling has also been identified and characterized during the progression of disease. Recent advances in understanding the cellular and molecular processes governing innervation and the functional control of the myocardium in health and disease provide a rational mechanistic basis for the development of neuraxial therapies for preventing sudden cardiac death and other arrhythmias. Advances in cellular, molecular, and bioengineering realms have underscored the emergence of this area as an important avenue of scientific inquiry and therapeutic intervention.
| S-EPMC4465108 | biostudies-literature
Project description: Not available
| S-EPMC4578227 | biostudies-literature
Project description:Arrhythmic sudden cardiac death (SCD) may be caused by ventricular tachycardia/fibrillation or pulseless electric activity/asystole. Effective risk stratification to identify patients at risk of arrhythmic SCD is essential for targeting our healthcare and research resources to tackle this important public health issue. Although our understanding of SCD because of pulseless electric activity/asystole is growing, the overwhelming majority of research in risk stratification has focused on SCD-ventricular tachycardia/ventricular fibrillation. This review focuses on existing and novel risk stratification tools for SCD-ventricular tachycardia/ventricular fibrillation. For patients with left ventricular dysfunction or myocardial infarction, advances in imaging, measures of cardiac autonomic function, and measures of repolarization have shown considerable promise in refining risk. Yet the majority of SCD-ventricular tachycardia/ventricular fibrillation occurs in patients without known cardiac disease. Biomarkers and novel imaging techniques may provide further risk stratification in the general population beyond traditional risk stratification for coronary artery disease alone. Despite these advances, significant challenges in risk stratification remain that must be overcome before a meaningful impact on SCD can be realized.
| S-EPMC4466101 | biostudies-literature
Project description:Sudden cardiac death (SCD), a sudden pulseless condition due to cardiac arrhythmia, remains a major public health problem despite recent progress in the treatment and prevention of overall coronary heart disease. In this review, we examine the evidence for genetic susceptibility to SCD in order to provide biological insight into the pathogenesis of this devastating disease and to explore the potential for genetics to impact clinical management of SCD risk. Both candidate gene approaches and unbiased genome-wide scans have identified novel biological pathways contributing to SCD risk. Although risk stratification in the general population remains an elusive goal, several studies point to the potential utility of these common genetic variants in high-risk individuals. Finally, we highlight novel methodological approaches to deciphering the molecular mechanisms involved in arrhythmogenesis. Although further epidemiological and clinical applications research is needed, it is increasingly clear that genetic approaches are yielding important insights into SCD that may impact the public health burden imposed by SCD and its associated outcomes.
| S-EPMC3501725 | biostudies-literature
Project description:Although the occurrence of sudden cardiac death (SCD) in a young person is a rare event, it is traumatic and often widely publicized. In recent years, SCD in this population has been increasingly seen as a public health and safety issue. This review presents current knowledge relevant to the epidemiology of SCD and to strategies for prevention, resuscitation, and identification of those at greatest risk. Areas of active research and controversy include the development of best practices in screening, risk stratification approaches and postmortem evaluation, and identification of modifiable barriers to providing better outcomes after resuscitation of young SCD patients. Institution of a national registry of SCD in the young will provide data that will help to answer these questions.
| S-EPMC5033115 | biostudies-literature
Project description:The prevention and treatment of sudden cardiac death (SCD) remains a significant public health challenge. For patients with a history of sudden death attributable to ventricular arrhythmia, implantable cardioverter-defibrillator (ICD) therapy is a mainstay of treatment, although these patients remain at high risk for recurrent ventricular arrhythmia and defibrillator therapies. In this review, we summarize landmark clinical trials evaluating the efficacy of ICD therapy in secondary prevention patients, review clinical outcomes including mode of death in survivors of SCD, and highlight the role for systematic diagnostic evaluation. We additionally discuss the invasive electrophysiological management of these patients, including ICD selection and programming as well as the role and timing of antiarrhythmic drug therapy and catheter ablation. Finally, we frame future challenges and needs to advance the care for secondary prevention patients.
| S-EPMC8183887 | biostudies-literature
Project description:Genetic conditions, even those associated with identical gene mutations, can present with variable clinical manifestations. One widely accepted explanation for this phenomenon is the existence of genetic factors capable of modifying the consequences of disease-causing mutations (modifier genes). Here, we address the concepts and principles by which genetic factors may be involved in modifying risk for cardiac arrhythmia, then discuss the current knowledge and interpretation of their contribution to clinical heterogeneity. We illustrate these concepts in the context of two important clinical conditions associated with risk for sudden cardiac death including a monogenic disorder (congenital long QT syndrome) in which the impact of modifier genes has been established, and a complex trait (life-threatening arrhythmias in acute myocardial infarction) for which the search for genetic modifiers of arrhythmic risk is more challenging. Advances in understanding the contribution of modifier genes to a higher or lower propensity towards sudden death should improve patient-specific risk stratification and be a major step towards precision medicine.
| S-EPMC6247660 | biostudies-literature
Project description:Purpose of reviewTo survey recent developments in the field of genetics encompassing discovery of new candidate genes, new diagnostic strategies, and new therapies for sudden cardiac death (SCD) syndromes.Recent findingsIn addition to new mutations in known SCD genes, several novel genes not previously implicated in SCD causation have been found, particularly in long QT syndrome (e.g., KCNJ5, AKAP9, SNTA1), idiopathic ventricular fibrillation (e.g., DPP6, KCNJ8), dilated cardiomyopathy (e.g., NEBL), and hypertrophic cardiomyopathy (HCM; e.g., NEXN). Genetic SCD animal models have provided novel insights into the cellular mechanism and pathogenesis of nearly all the major SCD syndromes, which has led to several new drug therapies for patients with genetic arrhythmia syndromes (e.g., flecainide in catecholaminergic polymorphic ventricular tachycardia). Furthermore, genetic contributions to acquired heart diseases are increasingly being recognized. For example, a 21q21 locus is strongly associated with ventricular fibrillation after myocardial infarction. Near this locus is CXADR, a gene encoding a viral receptor implicated in myocarditis and dilated cardiomyopathy. Finally, common variants in cardiac ion channels and proteins likely contribute to common cardiac phenotypes.SummaryMajor strides have been made in uncovering new genes, mechanisms, and syndromes that have significantly advanced the diagnosis and treatment of genetic SCD disorders.
| S-EPMC3145336 | biostudies-literature
Project description:BackgroundBlacks have a higher incidence of out-of-hospital sudden cardiac death (SCD) in comparison with whites. However, the racial differences in the cumulative risk of SCD and the reasons for these differences have not been assessed in large-scale community-based cohorts. The objective of this study is to compare the lifetime cumulative risk of SCD among blacks and whites, and to evaluate the risk factors that may explain racial differences in SCD risk in the general population.MethodsThis is a cohort study of 3832 blacks and 11 237 whites participating in the Atherosclerosis Risk in Communities Study (ARIC). Race was self-reported. SCD was defined as a sudden pulseless condition from a cardiac cause in a previously stable individual, and SCD cases were adjudicated by an expert committee. Cumulative incidence was computed using competing risk models. Potential mediators included demographic and socioeconomic factors, cardiovascular risk factors, presence of coronary heart disease, and electrocardiographic parameters as time-varying factors.ResultsThe mean (SD) age was 53.6 (5.8) years for blacks and 54.4 (5.7) years for whites. During 27.4 years of follow-up, 215 blacks and 332 whites experienced SCD. The lifetime cumulative incidence of SCD at age 85 years was 9.6, 6.6, 6.5, and 2.3% for black men, black women, white men, and white women, respectively. The sex-adjusted hazard ratio for SCD comparing blacks with whites was 2.12 (95% CI, 1.79-2.51). The association was attenuated but still statistically significant in fully adjusted models (hazard ratio, 1.38; 95% CI, 1.11-1.71). In mediation analysis, known factors explained 65.3% (95% CI 37.9-92.8%) of the excess risk of SCD in blacks in comparison with whites. The single most important factor explaining this difference was income (50.5%), followed by education (19.1%), hypertension (22.1%), and diabetes mellitus (19.6%). Racial differences were evident in both genders but stronger in women than in men.ConclusionsBlacks had a much higher risk for SCD in comparison with whites, particularly among women. Income, education, and traditional risk factors explained ≈65% of the race difference in SCD. The high burden of SCD and the racial-gender disparities observed in our study represent a major public health and clinical problem.
| S-EPMC6443438 | biostudies-literature
Project description:Hemodialysis patients carry a large burden of cardiovascular disease; most onerous is the high risk for sudden cardiac death. Defining sudden cardiac death among hemodialysis patients and understanding its pathogenesis are challenging, but inferences from the existing literature reveal differences between sudden cardiac death among hemodialysis patients and the general population. Vascular calcifications and left ventricular hypertrophy may play a role in the pathophysiology of sudden cardiac death, whereas traditional cardiovascular risk factors seem to have a more muted effect. Arrhythmic triggers also differ in this group as compared to the general population, with some arising uniquely from the hemodialysis procedure. Combined, these factors may alter the types of terminal arrhythmias that lead to sudden cardiac death among hemodialysis patients, having important implications for prevention strategies. This review highlights current knowledge on the epidemiology, pathophysiology, and risk factors for sudden cardiac death among hemodialysis patients. We then examine strategies for prevention, including the use of specific cardiac medications and device-based therapies such as implantable defibrillators. We also discuss dialysis-specific prevention strategies, including minimizing exposure to low potassium and calcium dialysate concentrations, extending dialysis treatment times or adding sessions to avoid rapid ultrafiltration, and lowering dialysate temperature.
| S-EPMC5457912 | biostudies-literature